"Atypical Antipsychotic Drugs in Alzheimer's Disease". The New England Journal of Medicine. Clinical Trials.gov number, NCT00015548.
Clinical Question
Do atypical antipsychotic drugs improve outcomes in outpatients with Alzheimer's disease who exhibit psychosis, aggression, or agitation?
Bottom Line
Adverse effects of atypical antipsychotic drugs may offset their potential advantages in efficacy for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease.
Major Points
While atypical antipsychotic drugs are commonly used to treat psychosis, aggression, and agitation in patients with Alzheimer's disease, their effectiveness remains uncertain, and safety concerns have emerged. This study aimed to assess the effectiveness of olanzapine, quetiapine, and risperidone against placebo in this patient group.
Guidelines
No specific guidelines were discussed in the article concerning the use of atypical antipsychotic drugs for the treatment of behavioral symptoms in Alzheimer's disease.
Design
- Multicenter, double-blind, placebo-controlled trial
- N=421 outpatients with Alzheimer's disease
- Interventions: olanzapine (mean dose 5.5 mg per day), quetiapine (mean dose 56.5 mg per day), risperidone (mean dose 1.0 mg per day), or placebo.
- Doses adjusted as needed, patients followed for up to 36 weeks
- Conducted between April 2001 and November 2004 across 42 sites in the United States
Population
- Inclusion criteria: Outpatients with dementia of the Alzheimer's type or probable Alzheimer's disease with psychosis, aggression, or agitation
- Exclusion criteria: Primary psychotic disorder, delirium, other dementia, psychosis, agitation or aggression from another medical condition, or contraindications to any of the study drugs
- Baseline Characteristics: Mean age 78 years, mean MMSE score 15, varied levels of care required
Interventions
- Olanzapine (mean dose, 5.5 mg per day)
- Quetiapine (mean dose, 56.5 mg per day)
- Risperidone (mean dose, 1.0 mg per day)
- Placebo
Outcomes
- The primary outcome was the time from initial treatment to the discontinuation of treatment for any reason.
- Secondary outcomes included the number of patients with improvement on the CGIC scale at 12 weeks and the median time to discontinuation due to lack of efficacy or due to adverse events/intolerability.
Criticisms
- Quetiapine's mean dose used was lower than in previous nursing home trials, possibly affecting outcomes.
- The design allowing patients to switch medications in phase 2 may have increased the rate of discontinuation in phase 1.
Funding
- The study was funded by the National Institute of Mental Health (NIMH).
- AstraZeneca Pharmaceuticals, Forest Pharmaceuticals, Janssen Pharmaceutica, and Eli Lilly donated drugs for the study but were not involved in design, analyses, or interpretation of results.
Further Reading
- The full article text on NEJM.org, ClinicalTrials.gov identifier NCT00015548.